Mirror-Image Dependence: Targeting Enantiomeric G-Quadruplex DNA Using Triplex Metallohelices

摘要

Natural D-DNA and L-DNA are mirror-image counterparts However, because of the inherent flexibility and conformation diversity of DNA, it is still not clear how enantiomeric compounds recognize D-DNA and L-DNA. Herein, taking G-quadruplex (G4) DNA as an example that has diverse conformations and distinct biofunctions, the binding of ten pairs of iron triplex metallohelices to D- and L-G4 DNA were evaluated. The Delta-enantiomer binds to n-DNA and the Lambda-enantionzer binds to L-DNA, exhibiting almost the same stabilization effect and binding affinity. The binding affinity of the Delta-metallohelix with D-G4 is nearly Delta-fold higher than that of Lambda-metallohelix binding D-G4. Delta-Metallohelix binding to D-G4 Pllows a two-step binding process driven by a favorable enthalpy contribution to compensate for the associated unfavorable entropy.